Inhibition of imipramine N-demethylation by fluvoxamine in Chinese young men
Abstract
AIM: To determine effect of fluvoxamine (Flu) on imipramine (lmi) N-demethylation in healthy Chinese subjects.
METHODS: The pharmaco-kinetic parameters of a single oral dose of lmi (100 mg) were compared before and during 2 wk coadministration of Flu (100 mg.d-1).
RESULTS: Flu resulted in a doubling of Cmax (112 +/- 33 vs 62 +/- 22 micrograms.L-1, P < 0.01) and an increase in AUC0- infinity (3.9 +/- 1.6 vs 1.5 +/- 0.6 mg.h.L-1, P < 0.01) of lmi. The T1/2 of lmi was prolonged (39 +/- 8 vs 23 +/- 7 h, P < 0.01) due to a marked reduction in Cl0 of lmi (0.6 +/- 0.3 vs 1.3 +/- 0.6 L.h-1.kg-1, P < 0.01). The Cmax of N-demethylated metabolite desipramine (Des) of lmi was decreased (10 +/- 2 vs 18 +/- 5 micrograms.L-1, P < 0.01) and AUC0- infinity of Des was reduced by 54% (0.61 +/- 0.20 vs 1.3 +/- 0.5 mg.h.L-1, P < 0.01) during coadministration with Flu.
CONCLUSION: Flu can markedly inhibit lmi N-demethylation in Chinese young men.
Keywords:
METHODS: The pharmaco-kinetic parameters of a single oral dose of lmi (100 mg) were compared before and during 2 wk coadministration of Flu (100 mg.d-1).
RESULTS: Flu resulted in a doubling of Cmax (112 +/- 33 vs 62 +/- 22 micrograms.L-1, P < 0.01) and an increase in AUC0- infinity (3.9 +/- 1.6 vs 1.5 +/- 0.6 mg.h.L-1, P < 0.01) of lmi. The T1/2 of lmi was prolonged (39 +/- 8 vs 23 +/- 7 h, P < 0.01) due to a marked reduction in Cl0 of lmi (0.6 +/- 0.3 vs 1.3 +/- 0.6 L.h-1.kg-1, P < 0.01). The Cmax of N-demethylated metabolite desipramine (Des) of lmi was decreased (10 +/- 2 vs 18 +/- 5 micrograms.L-1, P < 0.01) and AUC0- infinity of Des was reduced by 54% (0.61 +/- 0.20 vs 1.3 +/- 0.5 mg.h.L-1, P < 0.01) during coadministration with Flu.
CONCLUSION: Flu can markedly inhibit lmi N-demethylation in Chinese young men.